About BRCA2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
BRCA2 c.2471T>C, p.(Leu824Ser)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen BRCA2 VCEP v1.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 2
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 2
BP1Strong
BP1 · strong
This missense variant is outside the BRCA2 clinically important domains used by the ENIGMA specification, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.01, which is at or below the BP1_Strong threshold of 0.1. These findings support BP1_Strong.
BP6Supporting
BP6 · supporting
Expert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Likely benign.
Recorded classification: Likely benign
ENIGMA BRCA1/BRCA2 Specification v1.2 Table 3 final-classification framework from the official CSPEC/VCEP source.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
4 / 1,602,664 alleles
gnomAD v4.1: 4 / 1,602,664 alleles. Recorded AF 2.49584e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 8.41885e-06; MAF= 0.00084%, 2/237562 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000113507; MAF= 0.01135%, 2/17620 alleles, homozygotes = 0); grpmax FAF= 1.975e-05.
No listed criterion applied
No screenshot for this evidence
Computational predictions
Not recorded
No SpliceAI or REVEL score is recorded in the fields used for this tile.
No listed criterion applied
ClinVar submissions
Not recorded
A ClinVar laboratory submission summary was not recorded.
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed
No COSMIC evidence statement is recorded in this case.
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen BRCA2 VCEP v1.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 2 met · 15 not met · 3 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The BRCA2 c.2471T>C (p.Leu824Ser) variant has not been observed in COSMIC and has been reported in ClinVar, where the current expert-panel classification is likely benign.
This variant is present at low frequency in population databases, including 2/237562 alleles in gnomAD v2.1 and 4/1602664 alleles in gnomAD v4.1, with v2.1 grpmax FAF 1.975e-05 and v4.1 grpmax FAF 2.98e-05; these values are below the ENIGMA BA1 and BS1 thresholds and do not support PM2 because the variant is not absent from controls.
Computational evidence supports a benign interpretation under the BRCA2 ENIGMA framework because p.Leu824Ser lies outside the BRCA2 clinically important domains used for missense evaluation, SpliceAI predicts no significant splice effect with a maximum delta score of 0.01, BayesDel is -0.270943, and REVEL is 0.261, supporting BP1_Strong and not supporting PP3.
The BRCA2 clinical-history likelihood ratio is 0.60 in 2 probands, which falls in the neutral zone and does not support either PP4 or BP5.
No criteria match.
Met · 2
BP1 StrongThis missense variant is outside the BRCA2 clinically important domains used by the ENIGMA specification, and SpliceAI predicts no significant splice effect with a maximum delta score of 0.01, which is at or below the BP1_Strong threshold of 0.1. These findings support BP1_Strong. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP1_Strong applies to missense variants outside clinically important domains with SpliceAI ≤0.1.
Evidence considered
- Protein consequence p.(Leu824Ser) at residue 824.
- Residue 824 is outside BRCA2 PALB2 binding domain aa10-40 and DNA binding region aa2481-3186.
- SpliceAI max delta score 0.01 (≤0.1).
Sources
BP6 SupportingExpert panel ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen classified as Likely benign. Details ▾Hide ▴
Not met · 15 · evaluated, threshold not reached
PVS1 This missense variant does not fall into the BRCA2 PVS1 null-variant categories, and no RNA evidence showing a loss-of-function transcript effect was identified. Available evidence therefore does not support applying PVS1. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PVS1 applies to qualifying loss-of-function variants or RNA evidence demonstrating a damaging transcript effect.
Evidence considered
- BRCA2 loss of function is an established disease mechanism in the ENIGMA framework.
- NM_000059.3:c.2471T>C is a missense change encoding p.(Leu824Ser)
- not a nonsense
- frameshift
- or canonical ±1
- 2 splice variant.
- SpliceAI max delta score is 0.01
- which does not suggest a major splice effect.
Sources
PS3 No calibrated functional study result for BRCA2 p.(Leu824Ser) was identified in the reviewed BRCA2 functional resources, so available evidence does not support PS3. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS3 requires well-established functional evidence supportive of a damaging effect.
Evidence considered
- No exact match for c.2471T>C or p.(Leu824Ser) was identified in BRCA2 functional Table 9.
- OncoKB did not identify variant-specific reviewed functional evidence.
Still missing
- No exact-match calibrated functional assay result for c.2471T>C / p.(Leu824Ser) was identified in the reviewed BRCA2 functional datasets.
Sources
PS4 Available evidence does not show a statistically significant enrichment of this variant in affected individuals compared with controls, so PS4 is not met. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS4 requires significant case-control enrichment.
Evidence considered
- ClinVar shows mixed submissions with an expert-panel likely benign assertion
- but no PS4-level case-control evidence was verified.
- No exact match for this variant was identified in the reviewed BRCA2 supplementary or HUMU tables searched for PS4 support.
Still missing
- No case-control study with p-value ≤0.05 and odds ratio ≥4 for this variant was identified.
- No exact-match multifactorial enrichment result was identified in the reviewed BRCA2 supplementary datasets.
Sources
PM2 This variant is present in population databases, so it is not absent from controls. In gnomAD v2.1 it is seen at 2/237562 alleles with grpmax FAF 1.975e-05, and in gnomAD v4.1 it is seen at 4/1602664 alleles with grpmax FAF 2.98e-05; these findings do not support PM2. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM2_Supporting requires absence from gnomAD controls.
Evidence considered
- gnomAD v2.1: 2/237562 alleles
- total AF 8.418854867360941e-06
- grpmax FAF 1.975e-05.
- gnomAD v4.1: 4/1602664 alleles
- total AF 2.4958444190422947e-06
- grpmax FAF 2.98e-05.
Sources
PM5 This is a missense variant rather than a protein-truncating variant, and the BRCA2 ENIGMA PM5 rule in the reviewed materials is the PM5_PTC framework for qualifying truncating variants. Available evidence therefore does not support PM5. Details ▾Hide ▴
Rule
Reviewed ENIGMA BRCA2 PM5 evidence applies to qualifying PTC variants in eligible exons.
Evidence considered
- c.2471T>C encodes p.(Leu824Ser)
- a missense change.
- Reviewed BRCA2 Table 4 addresses PM5_PTC applicability for truncating variants by exon.
Sources
cspec ↗vcep_specifications_table4_v1_2_2024_11_18
PP1 No quantitative co-segregation data were identified for this variant, so available evidence does not support PP1. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP1 requires quantitative co-segregation evidence.
Evidence considered
- No pedigree-based LR or segregation dataset entry for this variant was verified from the reviewed materials.
Still missing
- No family-based segregation likelihood ratio meeting ENIGMA thresholds was identified.
Sources
PP3 Computational evidence does not meet the BRCA2 ENIGMA PP3 thresholds. SpliceAI predicts no meaningful splice effect with a maximum delta score of 0.01, below the PP3 splice threshold of 0.2, and this residue lies outside the BRCA2 clinically important domains used for missense PP3. BayesDel is -0.270943 and REVEL is 0.261, which do not provide VCEP support for PP3 here. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP3 requires either SpliceAI ≥0.2 or BayesDel no-AF ≥0.30 for a missense/in-frame variant inside a qualifying domain.
Evidence considered
- SpliceAI max delta score 0.01 (<0.2).
- Residue 824 is outside BRCA2 aa10-40 and aa2481-3186 ENIGMA functional domains.
- BayesDel no-AF score -0.270943.
- REVEL score 0.261.
Sources
PP4 The BRCA2 clinical-history likelihood ratio for this variant is 0.60 in 2 probands, which is below the ENIGMA PP4 supporting threshold of 2.08. This does not support PP4. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP4 uses multifactorial clinical-history likelihood ratios.
Evidence considered
- Clinical-history LR = 0.5995256450484732 from 2 probands.
- PP4 supporting requires LR ≥2.08.
Sources
BA1 Population frequency does not reach the BRCA2 ENIGMA BA1 threshold. The highest observed grpmax FAF is 1.975e-05 in gnomAD v2.1 and 2.98e-05 in gnomAD v4.1, both well below the BA1 threshold of 0.001. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BA1 requires FAF >0.1%.
Evidence considered
- gnomAD v2.1 grpmax FAF 1.975e-05.
- gnomAD v4.1 grpmax FAF 2.98e-05.
- BA1 requires FAF >0.001.
Sources
BS1 Population frequency does not meet the BRCA2 ENIGMA BS1 threshold in the reviewed evidence. In gnomAD v2.1 the grpmax FAF is 1.975e-05, which is below the BS1 supporting threshold of >2.0e-05 and far below the BS1 strong threshold of >1.0e-04. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS1 is based on gnomAD filter allele frequency thresholds.
Evidence considered
- gnomAD v2.1 grpmax FAF 1.975e-05.
- BS1 supporting requires FAF >2.0e-05
- BS1 strong requires FAF >1.0e-04.
Sources
BS3 No calibrated benign functional result for BRCA2 p.(Leu824Ser) was identified in the reviewed BRCA2 functional resources, so available evidence does not support BS3. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS3 requires well-established functional studies showing no damaging effect.
Evidence considered
- No exact match for c.2471T>C or p.(Leu824Ser) was identified in BRCA2 functional Table 9.
- OncoKB did not identify variant-specific reviewed functional evidence.
Still missing
- No exact-match benign functional assay result for c.2471T>C / p.(Leu824Ser) was identified in BRCA2 Table 9 or other reviewed BRCA2 functional resources.
Sources
BS4 No quantitative lack-of-segregation evidence was identified for this variant, so available evidence does not support BS4. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS4 requires quantitative lack-of-segregation evidence.
Evidence considered
- No verified BS4-specific segregation LR was identified for this variant.
Still missing
- No family-based non-segregation likelihood ratio meeting ENIGMA thresholds was identified.
- No exact-match entry supporting BS4 was verified in the reviewed BRCA2 supplementary datasets.
Sources
BP4 Although computational predictors do not suggest a damaging effect, BP4 is not applied here because the BRCA2 ENIGMA missense BP4 rule is restricted to variants inside the specified clinically important domains. This variant lies at residue 824, outside those domains, so BP4 is not met and the benign computational evidence is captured by BP1_Strong instead. Details ▾Hide ▴
Rule
For BRCA2 missense variants, ENIGMA BP4 requires location inside a qualifying domain plus BayesDel no-AF ≤0.18 and SpliceAI ≤0.1.
Evidence considered
- Residue 824 is outside BRCA2 aa10-40 and aa2481-3186 ENIGMA functional domains.
- SpliceAI max delta score 0.01 (≤0.1).
- BayesDel no-AF score -0.270943 (≤0.18).
- REVEL score 0.261.
Sources
BP5 The BRCA2 clinical-history likelihood ratio for this variant is 0.60 in 2 probands, which is above the ENIGMA BP5 supporting threshold of 0.48. This value falls in the neutral zone and does not support BP5. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP5 uses multifactorial clinical-history likelihood ratios.
Evidence considered
- Clinical-history LR = 0.5995256450484732 from 2 probands.
- BP5 supporting requires LR ≤0.48.
Sources
BP7 This is a missense variant, and no RNA study demonstrating a benign transcript effect was identified. Available evidence therefore does not support BP7. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP7 is reserved for specific RNA-based or silent/intronic scenarios.
Evidence considered
- Variant type is missense
- p.(Leu824Ser).
- SpliceAI max delta score 0.01 does not by itself fulfill the BRCA2 ENIGMA BP7 RNA evidence framework for a missense variant.
Still missing
- No exact-match benign RNA assay result for this variant was identified.
Sources
Not assessed · 3 · no assessment recorded
PS1 No same-amino-acid pathogenic or likely pathogenic comparator variant was verified for this amino acid change, so PS1 was not assessed from the available evidence. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PS1 requires a previously classified pathogenic or likely pathogenic variant with the same protein change or equivalent splicing effect.
Evidence considered
- ClinVar contains an expert-panel likely benign classification for this variant
- but no validated PS1 comparator was confirmed from the reviewed sources.
Still missing
- A verified BRCA2 variant causing the same amino acid change with an established pathogenic or likely pathogenic classification was not identified.
Sources
PM3 No evidence was identified that this variant was observed in trans with another BRCA2 variant in an individual with BRCA2-related Fanconi anemia, so PM3 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PM3 is reserved for qualifying BRCA2-related Fanconi anemia cases with point-based in-trans evidence.
Evidence considered
- No PM3-specific case-level evidence was identified in the reviewed materials.
Still missing
- No Fanconi-anemia phenotype data or qualifying in-trans observations were identified.
Sources
BS2 No point-based evidence was identified showing this variant in individuals without features of BRCA2-related Fanconi anemia under the ENIGMA BS2 framework, so BS2 was not assessed. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BS2 uses a point-based framework tied to absence of recessive disease features.
Evidence considered
- No BS2-specific case data were identified in the reviewed materials.
Still missing
- No qualifying BS2 point assignments or relevant phenotype observations were identified.
Sources
Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 N/AThe ENIGMA BRCA2 specification does not use PS2 for this gene framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- PS2 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
PM1 N/APM1 is not used in the ENIGMA BRCA2 specification for this framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- PM1 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
PM4 N/APM4 is not used in the ENIGMA BRCA2 specification for this framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- PM4 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
PM6 N/AThe ENIGMA BRCA2 specification does not use PM6 for this gene framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- PM6 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
PP2 N/AThe ENIGMA BRCA2 specification does not use PP2 for this gene framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- PP2 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
PP5 N/AThe ENIGMA BRCA2 specification does not use PP5 for this framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- PP5 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
BP2 N/AThe ENIGMA BRCA2 specification does not use BP2 for this gene framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- BP2 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
BP3 N/AThe ENIGMA BRCA2 specification does not use BP3 for this gene framework, so this criterion is not applicable. Details ▾Hide ▴
Rule
Not applicable in ENIGMA BRCA2 v1.2.
Evidence considered
- BP3 is marked not applicable in the BRCA2 ENIGMA specification.
Sources
Identifiers
- Gene
- BRCA2
- Transcript
- NM_000059.3
- Coding (HGVS c.)
- NM_000059.3:c.2471T>C
- Protein (HGVS p.)
- NP_000050.2:p.(Leu824Ser)
- GRCh38
- chr13:32336826 T>C
- GRCh37
- chr13:32910963 T>C
Gene diagram
Every interpreted variant in BRCA2, mapped onto the exon structure of NM_000059.3. Select a row to find it on the plot.
BRCA2NM_000059.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in BRCA2
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
4 / 1,602,664 alleles
AF 2.5e-06 · 0 homozygotes · FAF 2.98e-05
gnomAD v2.1
2 / 237,562 alleles
AF 8.42e-06 · 0 homozygotes · FAF 1.97e-05
By genetic ancestry
gnomAD v4.1
AF 2.5e-06 · 4 / 1,602,664 alleles · 0 hom · FAF 3e-05
| East Asian4 / 44,824 | 8.9e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 8.4e-06 · 2 / 237,562 alleles · 0 hom · FAF 2e-05
| East Asian2 / 17,620 | 0.00011 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.49584e-06; MAF= 0.00025%, 4/1602664 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 8.92379e-05; MAF= 0.00892%, 4/44824 alleles, homozygotes = 0); grpmax FAF= 2.98e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 8.41885e-06; MAF= 0.00084%, 2/237562 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000113507; MAF= 0.01135%, 2/17620 alleles, homozygotes = 0); grpmax FAF= 1.975e-05.
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 Computational evidence does not meet the BRCA2 ENIGMA PP3 thresholds. SpliceAI predicts no meaningful splice effect with a maximum delta score of 0.01, below the PP3 splice threshold of 0.2, and this residue lies outside the BRCA2 clinically important domains used for missense PP3. BayesDel is -0.270943 and REVEL is 0.261, which do not provide VCEP support for PP3 here. Details ▾Hide ▴
Rule
ENIGMA BRCA2 PP3 requires either SpliceAI ≥0.2 or BayesDel no-AF ≥0.30 for a missense/in-frame variant inside a qualifying domain.
Evidence considered
- SpliceAI max delta score 0.01 (<0.2).
- Residue 824 is outside BRCA2 aa10-40 and aa2481-3186 ENIGMA functional domains.
- BayesDel no-AF score -0.270943.
- REVEL score 0.261.
Sources
BP4 Although computational predictors do not suggest a damaging effect, BP4 is not applied here because the BRCA2 ENIGMA missense BP4 rule is restricted to variants inside the specified clinically important domains. This variant lies at residue 824, outside those domains, so BP4 is not met and the benign computational evidence is captured by BP1_Strong instead. Details ▾Hide ▴
Rule
For BRCA2 missense variants, ENIGMA BP4 requires location inside a qualifying domain plus BayesDel no-AF ≤0.18 and SpliceAI ≤0.1.
Evidence considered
- Residue 824 is outside BRCA2 aa10-40 and aa2481-3186 ENIGMA functional domains.
- SpliceAI max delta score 0.01 (≤0.1).
- BayesDel no-AF score -0.270943 (≤0.18).
- REVEL score 0.261.
Sources
BP7 This is a missense variant, and no RNA study demonstrating a benign transcript effect was identified. Available evidence therefore does not support BP7. Details ▾Hide ▴
Rule
ENIGMA BRCA2 BP7 is reserved for specific RNA-based or silent/intronic scenarios.
Evidence considered
- Variant type is missense
- p.(Leu824Ser).
- SpliceAI max delta score 0.01 does not by itself fulfill the BRCA2 ENIGMA BP7 RNA evidence framework for a missense variant.
Still missing
- No exact-match benign RNA assay result for this variant was identified.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.261. BayesDel score = -0.270943.
0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
4 / 1,602,664 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Captured SpliceAI source record
Open source ↗
ClinVar
Captured ClinVar source record
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1535438831
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/133734/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/13-32910963-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr13-32336826-T-C?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000059.3%3Ac.2471…
- OncoKB ↗www.oncokb.org/gene/BRCA2/L824S
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=BRCA2+c.2471T%3EC
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 2.49584e-06; MAF= 0.00025%, 4/1602664 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 8.92379e-05; MAF= 0.00892%, 4/44824 alleles, homozygotes = 0); grpmax FAF= 2.98e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 8.41885e-06; MAF= 0.00084%, 2/237562 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000113507; MAF= 0.01135%, 2/17620 alleles, homozygotes = 0); grpmax FAF= 1.975e-05.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories) and as Likely pathogenic (1 clinical laboratory) and as Uncertain Significance (1 clinical laboratory) and as Likely Benign by ClinGen ENIGMA BRCA1 and BRCA2 Variant Curation Expert Panel, ClinGen (expert panel).
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.261. BayesDel score = -0.270943.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. BRCA2, a tumor suppressor involved in the DNA damage response, is mutated in various cancer types.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.